Chlorhexidine (CHX) is a well-known antimicrobial which finds use in various medical applications. These include skin cleansing preparations, hand disinfectants and mouthrinses. CHX is a useful antimicrobial due to its efficacy against both Gram-positive and Gram-negative bacteria and many species of yeast. A further advantage over other antimicrobials is the desirable antibiotic resistance properties associated with CHX. Although individual microbe populations can become less sensitive to CHX when subjected to increasing environmental concentrations, studies have shown that this resistance is temporary and falls when the CHX stimulus is removed.
The systematic name for CHX is N′,N′″″-hexane-1,6-diylbis[N-(4-chlorophenyl)(imidodicarbonimidic diamide)] and it has the following chemical formula.

The most common CHX antimicrobial is an aqueous solution of the readily soluble salt CHX digluconate. The slightly less soluble salt CHX diacetate (CHA) has also been used, sometimes as a dry crystalline powder which is added to materials in order to confer some antimicrobial properties on those materials.
A problem with these CHX compounds is that when used in antimicrobial compositions they provide only very short-term delivery of aqueous CHX to the target areas. For example, in oral hygiene applications CHX digluconate may be delivered to the oral cavity in a mouthrinse, but within minutes the levels of CHX in this aqueous solution are severely depleted. A repeat of the treatment is necessary in order to maintain the delivery of sufficient levels of antimicrobial to the target area.
A further limitation is that the amount of CHX (e.g. the amount per unit surface area) that can be released from a treated substrate is limited and linked to the concentration of the CHX solution when surface treating with soluble CHX salts in solution, and therefore the antimicrobial efficacy of these solutions is also limited, not easily controllable, and may not be sufficient.
EP 2462960 A2 discloses a medical indwelling device such as a catheter having an antimicrobial agent. The device includes a base material which is a silicone-urethane copolymer and a bioactive agent such as CHX or a suitable pharmacological salt thereof, such as CHA. CHX is released from the base material at a rate dependent on the specific copolymer composition. Slow release of CHX is observed over a period of 14 days. However, the applications are limited to coatings on polymeric catheters because the base polymer is required to retain the CHX. Additionally, it would be desirable to provide extended release of CHX to an even greater extent.
US 2007/0212419 A1 discloses a nanocomposite biocompatible hydrogel (NCHG) containing a matrix gel, nanoparticles (NPs) and CHX for use in the treatment of periodontal infections. The NPs are polymeric, made from copolymerised 2-hydroxyethyl methacrylate (HEMA) and polyethyleneglycol dimethacrylate (PEGDMA). The same monomers are used to produce the crosslinked matrix. CHX digluconate is used as the active agent. The NPs absorb CHX and extended release over 200 hours is observed. Again, applications are limited by the presence of the matrix gel, and the release profile of the CHX is still unsatisfactory for some applications. The NCHG cannot be used to confer antimicrobial properties on existing medical articles or compositions.
The present invention addresses the problems discussed above by providing an antimicrobial micro- or nanoparticle (MNP) comprising a CHX salt. Some of the particular CHX salts proposed herein provide sparingly soluble MNPs which in some aspects display an excellent release profile for CHX over an extended period of months rather than simply days or weeks. In some embodiments the CHX MNPs described herein can release CHX gradually for longer than 80 days. Other CHX salts proposed herein have a shorter CHX release period but, over a few hours or days, release a very high dose of soluble CHX. In some aspects, the release of CHX from samples treated with MNPs of these CHX salts is faster and in larger amount than is achieved from samples treated only with a CHX solution. These faster-release aspects may be useful in decontamination applications or to treat particularly stubborn or acute infections or outbreaks. Furthermore, the MNPs can find use in a wide variety of applications such as coatings on or embedded within medical articles to confer additional antimicrobial properties, or as a component of a composite material which can be used to deliver steady doses of antimicrobial CHX to target areas over a long period of time by means of the gradual leaching of soluble CHX out of the antimicrobial MNPs, or to deliver higher doses of CHX much more quickly than is possible from samples treated with CHX solution. Additionally, the MNPs of the present invention may also exhibit delayed release profiles, or profiles where the release of CHX is triggered by changes in environmental conditions.